Our research is directed toward understanding basic cellular processes in corneal epithelium under conditions of degeneration and regeneration due to disease or injury. We plan to study by techniques of electron microscopy, cytochemistry, biochemical assay and electrophoresis (1) the role of lysosomal enzymes in corneal epithelial disease and (2) the microfilament system which develops during the migratory phases of corneal healing. Recently we discovered a previously undescribed mechanism of disease. Needle-shaped birefringent crystals develop in corneal epithelial lesions in tyrosine-fed rats. These crystals are bounded by a membrane, penetrate cell nuclei, and pass from one cell to another disrupting cells. We have some ultrastructural evidence that the crystals are sequestered within lysosomes eventually rupturing the lysosomes and cells. The extracellular release of lysosomal enzymes may result in cell sloughing, chemotaxis of polymorphonuclear leukocyte invasion and ulcer formation. These are features common to bacterial and viral corneal diseases. Tyrosine keratopathy in the rat provides a system for study of the involvement of lysosomal enzymes in corneal ulceration. Information derived from this model system can provide useful clinical data not only about tyrosinosis but other epithelial erosions and keratopathies. A second important observation made during our study of corneal disease in tyrosine-fed rats was the presence of microfilament bundles in cells that migrate to cover the corneal ulcer. Understanding the stimulus for the production of this contractile system in the transition of nonmigratory to migratory corneal epithelial cells is basic to understanding wound healing. We propose to study the genesis of this actin-myosin system in the transition from non-migratory to migratory cells. Because of its simplicity, accessibility and avascularity, the cornea represents an outstanding in vivo system for study of actin-myosin systems in non-muscle cell movement. BIBLIOGRAPHIC REFERENCES: Gipson, Ilene K., and Ronald A. Anderson. Actin filaments in normal and migrating corneal epithelial cells. Invest. Ophthalmol. 16: 161, 1977. Gipson, Ilene K., and Ronald A. Anderson. Filaments and corneal epithelial wound healing. J. Cell Biol. 70: 154a, 1976.